OICC Press International Journal of Nano Dimension 2228-5059 16 2 2025 04 01 Development and optimization of polymeric nanosponges for enhanced delivery of diflunisal in rheumatoid arthritis 10.57647/j.ijnd.2025.1602.16 EN Kiran Balasaheb Aher Department of Pharmaceutical Quality Assurance, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, India https://orcid.org/0000-0002-6719-0553 Shubham Bhosale Department of Pharmaceutical Quality Assurance, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, India https://orcid.org/0009-0001-9766-1846 Girija Balasaheb Bhavar Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, India https://orcid.org/0000-0001-5931-4109 Mohammad Habeeb Department of Pharmaceutics, Crescent School of Pharmacy, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai, India https://orcid.org/0000-0002-9834-2310 Huay Woon You Pusat PERMATA@Pintar Negara, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia https://orcid.org/0000-0003-0305-0911 Journal Article 2025 04 01 Rheumatoid arthritis damages the synovial membrane, and diflunisal, a nonsteroidal anti-inflammatory drug (NSAID) with poor solubility, faces delivery challenges. Nanosponges enhance diflunisals solubility improving its bioavailability; in addition it improved its stability and controls its release. Current research focuses on developing polymeric nanosponges (DIF-NS) through emulsion solvent evaporation, optimized by central composite design. The optimized DIF-NS were further loaded into a carbopol 940 gel (DIF-NS-gel) and evaluated. The optimized BNS showed spherical morphology, % CDR (Percentage cumulative drug release) of 84.9 ± 1.6 within 12 hours and % entrapment efficiency of 82.45 % ± 1.2, a % practical yield of 75 % ± 2.2 with a particle size of 120.1 ± 8.5   nm, zeta potential -29 ± 3.2 mv, and a PDI of 0.348± 0.015. The drug excipient compatibility study was carried out by using FTIR. The sharp peak obtained in the DSC and XRD proves the drug's crystalline nature. The DIF-NS-gel exhibited sustained release and enhanced ex-vivo permeation compared to plain diflunisal gel. In a CFA-induced rheumatoid arthritis rabbit model, it significantly reduced inflammation for a prolonged duration. These findings highlight its potential for effective long-term rheumatoid arthritis management.